We propose to study the molecular basis of antigenic variation in an animal lentivirus system, equine infectious anemia virus. The EIA virus system is an important one to study since very little is known concerning the process of antigenic variation of lentiviruses at a molecular level. The mode of variation that takes place in lentivirus infected individuals has particular importance with respect to the development of any feasible immunoprophylactic strategy for human immunodeficiency virus. The EIA virus system has some important advantages over the other lentivirus systems in that very evident clinical signs appear in an infected equine (fever, anemia & thrombocytopenia) at the time of appearance of each new antigenic variant. This property makes it very convenient to study the appearance of new antigenic variants in a sequential fashion. Specifically we plan to: 1) Determine the nucleotide sequence of the env gene region of our parental EIA virus. 2) Determine the nucleotide sequence of the env gene region of in vivo derived antigenic variants. 3) Establish a bank of monoclonal antibodies to the envelope proteins of EIA virus. 4) Probe the virion topography of parental and variant EIA virus strains with monoclonal antibodies. 5) Determine the cell types involved in virus replication and persistence in vivo. and 6) Determine whether antigenic variation and the clinical spectrum of the natural disease in ponies can arise from a single molecularly cloned virus variant. We feel that these studies should lead to a more complete understanding of the process by which EIA virus variants appear in persistently infected animals. These new variants replicate in the animal to high titers even in the face of a previous immune response to the viral envelope proteins. The sequential appearance of new variants of HIV in infected humans may be an important part of the progression of this complex disease and our studies should help clarify this process.